Mitochondria Coordinate Sites of Axon Branching through Localized Intra-axonal Protein Synthesis

• Mitochondria and translational machinery are at sites of axon branching
• Mitochondria respiration is linked to sites of preferential axonal protein synthesis
• Mitochondria respiration promotes filopodial dynamics and branching
• Maturation of filopodia into branches requires mitochondrial respiration

SummaryThe branching of axons is a fundamental aspect of nervous system development and neuroplasticity. We report that branching of sensory axons in the presence of nerve growth factor (NGF) occurs at sites populated by stalled mitochondria. Translational machinery targets to presumptive branching sites, followed by recruitment of mitochondria to these sites. The mitochondria promote branching through ATP generation and the determination of localized hot spots of active axonal mRNA translation, which contribute to actin-dependent aspects of branching. In contrast, mitochondria do not have a role in the regulation of the microtubule cytoskeleton during NGF-induced branching. Collectively, these observations indicate that sensory axons exhibit multiple potential sites of translation, defined by presence of translational machinery, but active translation occurs following the stalling and respiration of mitochondria at these potential sites of translation. This study reveals a local role for axonal mitochondria in the regulation of the actin cytoskeleton and axonal mRNA translation underlying branching.

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